A study published in mSystems used shotgun metagenomic sequencing to examine links between the gut microbiome and coronary artery disease (CAD), identifying microbial species and metabolic pathways that differ between adults with CAD and matched controls. The analysis included stool samples from 14 individuals with CAD and 28 controls, generating metagenome-assembled genomes (MAGs) to provide strain-level resolution.
Across all samples, 520 bacterial species were detected. Fifteen were significantly associated with CAD status. Several Lachnospiraceae species were enriched in CAD, while multiple short-chain fatty acid (SCFA)–producing bacteria – such as Faecalibacterium prausnitzii, Slackia isoflavoniconvertens, and members of Catenibacterium – were depleted. SCFA-producing organisms have been linked to intestinal barrier stability and down-regulation of systemic inflammation, both relevant to cardiovascular risk. The species Prevotella copri_A was also reduced in CAD cases.
Further analysis showed differences in ten metabolic pathways. CAD samples displayed higher activity in the urea cycle, L-citrulline biosynthesis, glycolysis, and CDP-diacylglycerol biosynthesis. In contrast, pathways associated with SCFA and branched-chain amino acid biosynthesis were reduced. Additional module-level analysis suggested increased potential in CAD samples for degradation of aspartate, serine, arginine, lactose, and xylose – changes associated with production of pro-inflammatory metabolites.
Predicted metabolite profiling identified three metabolites that differed between groups. Inosine was elevated in CAD samples; two others (C18:0e MAG and α-muricholate) were lower. Although their diagnostic relevance is not yet established, inosine has known vascular activity and may influence coronary physiology.
Modelling showed that microbial species alone could distinguish CAD from controls with an AUC of 0.79. A metabolite-only model performed similarly, and a combined model achieved an AUC of 0.89, indicating the potential value of integrated microbiome-based biomarker panels.
Twenty-five microbial species were identified as having functional signatures distinct to CAD samples. Genomes from CAD samples showed enrichment of nitrogen fixation, CO reduction, and sulfite reduction – pathways associated with inflammatory dysbiosis. Control-derived genomes were enriched for functions such as aromatic degradation and iron reduction, indicating more stable metabolic profiles. Strain-level differences within species such as Akkermansia muciniphila and Megamonas fumiformis highlight functional variability that would be missed by species-level analysis alone.
WHile the study’s sample size was small, the findings show that metagenomic profiling can detect microbial and functional patterns associated with CAD. The results suggest that specific microbial pathways and metabolites may contribute to future biomarker discovery efforts aimed at identifying cardiovascular risk linked to gut microbiome alterations.
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